The technical field of this invention concerns medical devices useful for the repair of severed nerves and methods for fabricating and using such devices for nerve repair.
The problem of repairing severed nerves is a long-standing one that has plagued surgeons for over a hundred years. Despite advances in microsurgical techniques, the recovery of a patient from a serious wound is often limited by the degree of nerve damage which cannot be repaired. The replanting of amputated fingers and limbs is especially limited by poor nerve regeneration.
When a nerve is severed, the functions supplied by that nerve, both motor and sensory, are lost. The appendages of the nerve cells, or axons, in the distal regions of the severed nerve, or those areas furthest from the spinal cord, degenerate and die, leaving only the sheaths in which they were contained. These sheathes, too, degenerate with time. The axons in the proximal stump that remain connected to the spinal cord or dorsal root ganglion also suffer some degeneration.
However, degeneration generally does not proceed to the death of all of the nerve cell bodies. Moreover, if the injury occurs far enough from the nerve cell bodies, regeneration will occur. Axonal sprouts will appear from the tip of the regenerating axon. These sprouts grow distally and attempt to reenter the intact neurilemmal sheaths of the distal portion of the severed nerve. If entry is successfully made, axonal growth will continue down these sheaths and function will eventually be restored.
In the conventional approach to nerve repair, an attempt is made to align the cut ends of the fascicles (nerve bundles within the nerve trunk). A similar approach is taken with smaller nerves. In either case, the chief hazard to the successful repair is the trauma produced by the manipulation of the nerve ends and the subsequent suturing to maintain alignment. The trauma appears to stimulate the growth and/or migration of fibroblasts and other scar-forming connective tissue cells. The scar tissue prevents the regenerating axons in the proximal stump from reaching the distal stump to reestablish a nerve charge pathway. The result is a permanent loss of sensory or motor function.
Various attempts have been made over the years to find a replacement for direct (i.e., nerve stump-to-nerve-stump suturing). Much of the research in this field has focused on the use of "channels" or tubular prostheses which permit the cut ends of the nerve to be gently drawn into proximity and secured in place without undue trauma. It is also generally believed that such channels can also prevent, or at least retard, the infiltration of scar-forming connective tissue.
For example, the use of silastic cuffs for peripheral nerve repair was reported by Ducker et al. in Vol. 28, Journal of Neurosurgery. pp. 582-587 (1968). Silicone rubber sheathing for nerve repair was reported by Midgley et al. in Vol. 19, Surgical Forum. pp. 519-528 (1968) and by Lundborg et al. in Vol. 41, Journal of Neuropathology in Experimental Neurology, pp 412-422 (1982). The use of bioresorbable, polyglactin mesh tubing was reported by Molander et al. in Vol. 5, Muscle & Nerve. pp. 54-58 (1982). The use of porous acrylic copolymer tubes in nerve regeneration was disclosed by Uzman et al. in Vol. 9, Journal of Neuroscience Research. pp. 325-338 (1983). Bioresorbable nerve guidance channels of polyesters and other polymers have been reported by Nyilas et al. in Vol. 29, Transactions Am. Soc. Artif. Internal Organs. pp. 307-313 (1983) and in U.S. Pat. No. 4,534,349 issued to Barrows in 1985.
Despite the identification of various materials which can serve as nerve guidance channels, the results of research to date have revealed significant shortcomings in such prostheses. For example, some of the materials identified above have lead to inflammatory reactions in the test animals and have failed to exclude scar tissue formation within the channels. The total number of axons, the number of myelinated axons, the thickness of the epineurium, and the fascicular organization of nerves regenerated within guidance channels are all typically less than satisfactory and compare poorly with the original nerve structure of the test animals. Moreover, the loss of sensory or motor function is still the most common outcome of such laboratory experiments. In addition, if the gap distance separating the nerve stumps is too great, regeneration will not occur.
Channels have been manipulated in various ways in an attempt to correct these shortcomings. For example, channels prefilled with a laminin gel (as disclosed in Madison et al., Vol. 44, Brain Res., pp. 325-334 (1985)), a glycosaminoglycan template (as described in Yannas et al., Vol. 11, Trans. Soc. Biomat., pp. 146 (1985)), or with fibrin (Williams et al., Vol. 264, J. Como. Neurol. pp. 284-290 (1987)) have been used to enhance the regeneration of nerve ends separated by a gap distance greater than 10 mm. However, because these substances are normally substrate-bound materials, their conformation and, hence, their level of activity is decreased when they are solubilized.
Channels have also been preloaded with various growth factors (Politis et al., Vol. 253, Brain Res. pp. 1-12 (1982)). However, these factors typically are not stable in an aqueous environment; their half lives are measured in hours rather than in weeks, which is the least amount of time usually required for completed regeneration. In addition, the delivery of these factors is not continuous or controlled; it is dispensed as a one time bolus which is not conducive for long term nerve growth stimulation.
There exists a need for a better materials and methods for formation of nerve guidance channels. Materials and methods for nerve repair that would minimize surgical trauma, maximize distances over which nerves can regenerate, prevent interference with nerve growth by scar tissue and improve the chances for successful recovery of sensory or motor function would satisfy a long-felt need in this field.